Eco-friendly polyurethane acrylate (PUA)/natural filler-based composite as an antifouling product for marine coating.

In the current study, the polyurethane acrylate (PUA) polymer was synthesized by the addition reaction between an isophorone diisocyanate (IPDI) and 2-hydroxyethyl acrylate and cured by polyol. Different properties of the synthesized PUA were determined through diverse analysis methods. The polyurethane acrylate (PUA)/natural filler-based composite (rhizome water extract of Costus speciosus) was prepared as an antifouling agent. The results revealed that the lowest weight loss percentages were detected at 2 wt% PUA/natural filler composite loadings with Escherichia coli (ATCC 23,282) and Pseudomonas aeruginosa (ATCC 10,145). The decreased weight loss percentage may be attributed to the well dispersed natural composite resulting in a slippery surface that can prevent fouling adhesion. It was concluded that the PUA/natural filler composite might be considered an eco-friendly and economical solution to the biofouling problem. KEY POINTS: • A novel strategy for anti-biofouling. • A new composite reduced Gram-negative bacteria.

Stabilization of a hyaluronate-associated gene delivery system using calcium ions.

A "DPH" ternary complex consisting of plasmid DNA (pDNA), intracellularly degradable polyethyleneimine, and hyaluronic acid (HA) is a promising non-viral gene carrier with low toxicity and good gene transfection efficiency. HA plays a key role in providing an optimal balance between DNA protection and release, but it causes aggregation due to the entanglement of HA chains of neighbouring DPH particles. Here we report that the addition of an optimal level of Ca2+ successfully prevents particle aggregation and maintains a relatively small size. The Ca-stabilized DPH is comparable to DPH in cytotoxicity and gene transfection efficiency. MW monitoring and conductometric titration suggest that such size stabilization effect is partly mediated by the complexation between HA and Ca2+, which enables intra- and intermolecular interactions of HAs.

A strategy to deliver genes to cystic fibrosis lungs: a battle with environment.

Cystic fibrosis (CF) sputum, a tenacious biopolymer network accumulating in the airways, critically interferes with the effectiveness of pulmonary gene delivery. To overcome this challenge, nanoparticulate ternary gene-polymer complexes were encapsulated in inhalable dry microparticles containing mannitol. When applied on a layer of artificial sputum, which comprised major components of CF sputum such as DNA and mucin, mannitol microparticles rapidly dissolved in it and enhanced transport of nanoparticles across the sputum layer. Despite the improvement of nanoparticle transport in the artificial sputum, the gene-polymer complex passing the sputum did not show gene transfection because of the significant inactivation by DNA and, to a lesser extent, mucin. Particle size measurement suggested that aggregation of the gene transfer agents was mainly responsible for the activity loss. These results indicate that the delivery of gene transfer agent across CF sputum depended not only on the ability to penetrate the sputum but also on preservation of the activity during and/or after the transport.

Challenges and advances in the development of inhalable drug formulations for cystic fibrosis lung disease.

INTRODUCTION: Cystic fibrosis (CF) is a multisystem genetic disorder, which usually results in significant respiratory dysfunction. At present there is no cure for CF, but advances in pharmacotherapy have gradually increased the life expectancy of CF patients. As many drugs used in the therapy of CF are delivered by inhalation, the demand for effective and convenient inhalational CF drug formulations will grow as CF patients live longer. Knowledge of the current limitations in inhalational CF drug delivery is critical in identifying new opportunities and designing rational delivery strategies. AREAS COVERED: This review discusses current and emerging therapeutic agents for CF therapy, selected physiological challenges to effective inhalational medication delivery, and various approaches to overcoming these challenges. The reader will find an integrated view of the known inhalational drug delivery challenges and the rationales for recent investigational inhalational drug formulations. EXPERT OPINION: An ideal drug/gene delivery system to CF airways should overcome the tenacious sputum, which presents physical, chemical and biological barriers to effective transport of therapeutic agents to the targets and various cellular challenges.

Development of inhalable dry powder formulation of basic fibroblast growth factor.

Basic fibroblast growth factor (bFGF) is a promising agent for therapy of asthma or chronic obstructive pulmonary disease. We aim to develop an inhalable powder formulation of bFGF, which may provide a safe, effective, and convenient way of delivering bFGF to the disease-ridden lungs. Development of a bFGF dry powder formulation is constrained by the poor stability of bFGF and the uncertainty in compatibility of the protein with carrier excipients. With these constraints in mind, we prepared dry powders containing bFGF in combinations of albumin, phospholipid, lactose, and/or leucine, by spray drying, and evaluated the aerodynamic properties of the powders and the stability of bFGF loaded in the powders. While an ethanolic solution of phospholipid, albumin, and lactose produced dispersible powder, bFGF was unstable in ethanol. The stability of bFGF was preserved when spray-dried with lactose in an aqueous solution. Leucine was required to obtain dry powder with good dispersibility; however, increase in the leucine content more than 50% (w/w) negatively influenced the bFGF stability with no additional benefit to the aerodynamic properties of the powders. Dry powders containing 20% (w/w) leucine provided desirable aerodynamic properties (fine particle fraction of 25.2+/-5.4% and mass median aerodynamic diameter of 4.7+/-0.9 microm) and 98.1+/-7% recovery of bioactive bFGF. This result warrants further investigation of the biological activity of the inhaled bFGF in a disease model.